Dendritic cells (DC) are professional antigen-presenting cells (APC) that are believed to be indispensable to initiate a primary immune response (1,2). DC are migratory cells that exhibit complex trafficking properties in vivo, involving interaction with vascular and lymphatic endothelium and extracellular matrix (ECM). DC progenitors from the bone marrow enter the blood and seed nonlymphoid tissues. DC are spread all over the body, at epithelia (skin epidermis, airways, gastrointestinal, and genitourinary tracts) and at interstitial spaces of many solid organs (heart, liver, kidney), where they act as sentinels, waiting for an encounter with an antigen (1-3).

The mannose receptor (CD206) is involved in initiation and orientation of the immune response and distributed mostly on early pregnancy decidual macrophages surrounding glands. The effects of glandular mucin Tumor Associated Glycoprotein-72 (TAG-72) on decidual macrophages was evaluated. Binding and internalization of TAG-72 were measured by labelling of CD206 with PAM-1 monoclonal antibody or by FITC-Dextran uptake, respectively, in untreated or TAG-72 treated macrophages. The expression of maturation markers and cytokines were analyzed by flow cytometry, as well as the IL-4 protein expression in cord blood T cells after co-culture with purified decidual CD14+ cells untreated or treated with TAG-72. TAG-72 can be bound and internalized by the carbohydrate recognition domain of CD206. It up-regulates CD86 expression, IL-4 and IL-10 cytokine production in decidual macrophages and their capability to support IL-4 production in cord blood T cells. TAG-72 is the natural ligand for the carbohydrate recognition domain of CD206 on early decidual macrophages involved in supporting distinct profile of cytokine secretion, leading to pregnancy success. The investigation was supported by grants of Croatian Ministry of Science No. 0062029 and EMBIC project No. 512040, LSHM-CT-2004-512040.

CC chemokine ligand 1 (CCL1; I-309) is a CC chemokine that interacts with CC chemokine receptor 8, which is preferentially expressed in polarized T helper cell type 2 and Tc2 cells, in eosinophils, and in T regulatory cells. The present study, prompted by transcriptional profiling of human monocytes undergoing different forms of activation, was designed to characterize the production of CCL1 in monocytes compared with the production of other chemokines (CCL2, CCL22, and CCL18) differentially regulated by distinct activation signals. Lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), interleukin (IL)-1beta, tumor necrosis factor alpha, IL-4, IL-13, IL-10, IL-6, IL-18, and combinations thereof did not induce CCL1 production in monocytes, and some of these signals stimulated production of reference chemokines. Induction of CCL1 in monocytes required engagement of Fc receptor for immunoglobulin G (FcgammaR)II and exposure to IL-1beta or LPS. This combination of stimuli results in a form of M2 (M2b, Type 2) macrophage activation. FcgammaR engagement also induced CCL22 and amplified its stimulation by IL-4. In contrast, FcgammaR stimulation inhibited the IL-10- and LPS-mediated induction of CCL18. IL-10, IL-4, and IFN-gamma inhibited induction of CCL1 by FcgammaR ligation and IL-1beta. CCL1 was present in synovial fluids and macrophages in juvenile idiopathic arthritis. Thus, regulation of CCL1 in human monocytes is unique, with an obligate requirement of FcgammaR engagement and costimulation by signals (IL-1beta and LPS), which use the myeloid differentiation primary-response protein 88 adaptor protein. Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity.

The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.

After the identification of the interleukin (IL)-1 type II receptor as the prototype, decoy receptors have been identified for a number of members of the IL-1/IL-18, TNF, IL-10 and IL-13 receptor families. Moreover, the silent receptor D6 is a promiscuous decoy and scavenger receptor of inflammatory chemokines. The IL-1 decoy receptor is regulated by pro- and anti-inflammatory signals and its levels may serve as a readout of the activation of anti-inflammatory pathways, for instance by glucocorticoid hormones. Decoy receptors represent a strategy to tune inflammatory and polarized adaptive responses.

Pentraxins are a family of evolutionarily conserved multifunctional pattern-recognition proteins characterized by a cyclic multimeric structure. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver in response to IL-6, while PTX3 is produced by a variety of tissues and cells and in particular, by innate immunity cells in response to proinflammatory signals and Toll-like receptor (TLR) engagement. PTX3 interacts with several ligands, including growth factors, extracellular matrix components and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes, acting as a predecessor of antibodies. In addition, PTX3 is essential in female fertility by acting as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix. Thus, the prototypic long pentraxin PTX3 is a multifunctional soluble pattern recognition receptor acting as a nonredundant component of the humoral arm of innate immunity and involved in tuning inflammation, in matrix deposition and female fertility. Keywords: Pentraxins, innate immunity, inflammation, marker

SUMMARY Following a request from the European Commission, the European Food Safety Authority (EFSA) was asked to issue an opinion on the proposal made by the applicant for reducing the minimum content of monensin sodium (Mo-Na) from Coxidin ® 25% in complete feedingstuffs for turkeys from the current 90 mg kg -1 to 60 mg kg -1 . Five floor pen studies on turkeys for fattening were provided by the applicant. In four studies, growth and feed to gain ratio was improved, after four weeks, by 60 mg Mo-Na from Coxidin ® kg -1 complete feedingstuff. In the following four-week period, comparable effects could be observed for growth rate, but not for feed to gain ratio. Clinical endpoints, indicative for coccidiosis control, were with one exception (intestinal lesion score seven days after inoculation in two studies) not influenced. Coccidiosis in turkey is commonly milder than in chicken, this may contribute to explaining the lack of conclusive clinical data in these studies. Cumulative data (after 84 days for female and 112 days for male turkeys) showed positive effects for 60 mg Mo-Na from Coxidin ® kg -1 complete feedingstuff for growth and feed to gain ratio in one study, for feed to gain ratio and reduced mortality in another study, and reduced mortality alone in a third study. Based on these three studies, 60 mg Mo-Na from Coxidin ® kg -1 complete feedingstuff are considered as effective in floor pen trials.

The pariparoba (Piper cernuum Vell.), a native plant from the Atlantic Tropical Forest (ATF), has been commonly used in folk medicine. Works seeking the exploitation of P. cernuum natural populations need to be accomplished, seeking compatibility in obtaining income rates and preservation of ATF. The present work aimed to study the reproductive phenology and seed dispersal in P. cernuum natural population in the counties of Sete Barras/SP (Parque Estadual Intervales PEI). The population of P. cernuum studied in PEI presented continuously bud-inflorescences, green-infrutescences and bud-inflorescence emission, with variation among individuals. Fruit-set average was of 9.1%, varying among individuals. Shading and foliar damage presented negative effect on the fruit-set. Three species of bats were identified as potential dispersors of the P. cernuum seeds: Carollia perspicillata, Anoura geoffroyi and Artibeus sp. The foragement strategy observed was the withdrawal of some seeds per infrutescence per flight. This strategy increases the potential in establishing new plants as well as in increase the potential of gene flow in comparison with the entire infrutescence plant eaten at the night perches. In consequence, the results of reproductive phenology and seed dispersal ecology presented in this work can help to establish management and conservation strategies of P. cernuum natural populations in the ATF.

These findings demonstrate that immunosuppressive agents differently modulate the CKR switch associated with maturing DC; in particular, RAPA selectively up-regulates CCR7 and enhances the migration of differentiated DC to regional LN. This study contributes to a better understanding of the role of immunosuppressive therapy on DC migration, a potentially relevant check point of immunosuppressive treatment.

Chemokines play a key role in immune processes by controlling leukocyte recruitment in physiological and pathological condition. This review discusses the regulation of the chemokine system, its role in human diseases, and its potential relevance as a new pharmacological target.

The problem of the interference of celiac disease (CD) with the male reproductive system is made evident both by the recognized adverse effects on female reproduction and by the multifactorial nature of the disease. It is important to consider CD as a multifactorial condition since its diverse effects can be modulated, besides gluten, by different concurrent genetic and environmental factors. The male CD patient has a greater risk of infertility and other reproductive disturbances, as well as a greater incidence of hypoandrogenism. In this paper the problems of CD associated to endocrine disorders and to deficiencies of micronutrients are discussed. Affected males show a picture of tissue resistance to androgens. Moreover, attention should be paid to increases of FSH and prolactin; these are not associated to infertility and/or impotence, but they may indicate an imbalance at hypothalamus-pituitary level, with general effects on health: an example is the increased risk of male osteoporosis in CD patients. Hormone alterations are reversible upon start of the gluten-free diet, emphasizing the importance of early diagnosis; this should be performed in the case of clinical suspicion, e.g., unexplained hypoandrogenism. As regards nutritional aspects, the folic acid deficiency of CD can affect rapidly proliferating tissues, such as the embryo and the seminiferous epithelium. More attention should be paid to deficiencies of fat-soluble vitamins, such as A and E, observed in CD. Vitamin A is important for Sertoli cell function as well as for early spermatogenetic phases. Vitamin E supports the correct differentiation and function of epidydimal epithelium, spermatid maturation and secretion of proteins by the prostate. Therefore, CD male patients should be considered as vulnerable subjects; thus, the detection of early biomarkers of andrological or endocrinological dysfunctions should trigger timely strategies for prevention and treatment.

Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs that coordinate expression of genes involved in oxygen delivery (via angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand. CXCR4 induction by Hyp is dependent on both activation of the Hyp-inducible factor 1 alpha and transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 alpha-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments.